The immune response evolved to be inherently adaptable depending on the challenges it meets. In some instances, pregnancy for example, the immune response is reduced and tolerates immunological triggers or insults. In other instances, a microbial infection for example, the immune response is strong and allows the return to an homeostatic state.
However, in some individuals the immune balance is pathologically tipped either towards inflammation (e.g., a pro-inflammatory state, as observed in autoimmune diseases for example) or anergy (e.g., a pro-tolerogenic state, as observed in proliferation associated disorders for example) which leads to the onset of various conditions which may be long-lived and detrimental to the afflicted individuals. In order to mitigate such conditions, various therapeutics have been designed to restore an immune balance which will limit or prevent the pathological consequences associated with the onset of such conditions.
Therapeutics that are capable of restoring the immune balance, and more specifically capable of modulating the ratio of T regulatory (Treg) cells to pro-inflammatory T cells, have been described. A first class of biological therapeutics has been designed to decrease the ratio of Treg/pro-inflammatory cells in order to intentionally induce a more inflammatory immune state in individuals having a low or inappropriate immune response (refer to, for example, PCT patent applications PCT/CA2013/050546 (published under WO2014/008611) and PCT/CA2013/050963). These biological therapeutics are especially useful in mediating therapeutic benefits in individuals afflicted by a proliferation-associated disorder such as cancer. Other biological therapeutics have been designed to increase the ratio of Treg/pro-inflammatory T cells to intentionally induce a more tolerogenic immune state in individuals having an exacerbated immune response (refer to, for example, U.S. patent application Ser. No. 13/941,303 (published under US 2014/0017218), PCT patent applications PCT/CA2013/050547 (published under WO2014/008612), PCT/CA2013/050543 (published under WO2014/008608), PCT/CA2013/050544 (published under WO2014/008609) and PCT/CA2013/050545 (published under WO2014/008610)). This second class of biological therapeutics can provide therapeutic benefits in individuals afflicted by an auto-immune disease or at risk of rejecting a graft.
Even though some of the biological therapeutics have been show to induce long-lived beneficial immune modulating effects in individuals having received them, there exists a need for further modulating the immune response in some situations. For example, while providing therapeutic benefits to individuals afflicted by an auto-immune disease (by intentionally inducing a pro-tolerogenic immune state), these biological therapeutics also impede the immune response of the treated individuals towards a vaccine. As such, it may be beneficial for individuals having received biological therapeutics intentionally inducing a pro-tolerogenic state to have the ability, at least temporarily, to mount a robust immune response against an immunogen, such as the components of a vaccine. In another example, individuals having received a biological therapeutic intentionally inducing a pro-inflammatory state to favor tumor resorption could also benefit from a more pro-tolerogenic state prior to a tissue or a cell graft. As such, it may be beneficial for individuals having received biological therapeutics intentionally inducing a pro-inflammatory state to have the ability, at least temporarily, to avoid mounting an immune response against a grafted tissue or a transplanted cell.
It would be highly desirable to be provided with therapeutic combinations capable of modulating the immune response in an individual to provide immune stimulation when a pro-tolerogenic immune state was intentionally induced or immune tolerance when a pro-inflammatory immune state was intentionally induced. In some embodiments, it would also be highly desirable for some individuals to revert back to the intentionally induced pro-tolerogenic immune state or the intentionally induced pro-inflammatory immune state.